?PROJECT SUMMARY People living with chronic pain or illness are at increased risk of premature morbidity and mortality. The course of all chronic illnesses is affected by disease-related and life stress. Stress often leads to anxiety and depression, disturbs neuroendocrine and immune function, triggers unhealthy behaviors, and undermines adherence to medical recommendations. To alleviate the harmful effects of stress, behavioral interventions have been developed for people living with chronic pain and illness. Primary-level research indicates that behavioral interventions can reduce anxiety and depression but such research often has not had the statistical power needed to determine alternative outcomes (e.g., treatment adherence, health behavior change), mediating mechanisms (e.g., neuroendocrine and immunological markers), and moderators of intervention efficacy (e.g., patient or disease characteristics). With the recent surge in published research on complementary and behavioral medicine approaches, the literature is now large enough to permit an integrated meta-analytic investigation, which will have considerably more statistical power. Therefore, the proposed research will use meta-analytic methods to gauge the efficacy of stress management interventions to improve hypothesized biomarkers, treatment adherence, health behaviors, and disease progression as well as psychological outcomes. We will include research conducted with people living with (a) chronic pain or (b) three chronic diseases, specifically cardiovascular disease, diabetes, and HIV. The proposed meta-analytic research will further our understanding of the efficacy of behavioral stress management interventions in the context of chronic pain and illness, and help to guide future research toward important unanswered questions. The proposed meta-analytic research will also yield results that can help to guide health care providers, insurers, and policy makers who need precise information to make empirically-derived decisions about the optimal content and duration of an intervention, who is most likely to benefit, and how results may vary across chronic pain and disease conditions. Innovative aspects of the proposed research from this well-qualified and highly experienced team include (a) use of state-of-the science meta-analytic methods to integrate a large and complex literature, (b) precise measurement of the psychological, neuroendocrine, and immunological benefits accruing from behavioral stress management interventions, (c) identification of mediators and moderators of intervention efficacy, and (d) comparison of benefit across chronic pain and diseases. The research is highly significant because of the prevalence, impact, and cost of chronic pain and illness, the ubiquity of stress, and the need for effective stress management interventions for multiple chronic conditions. The long-term goal of this research is to guide the development of more powerful, efficient, and cost-effective stress management interventions for people living with one or more chronic conditions.